The overall goal of the research is to determine how light-evoked signals in the retina are formed and how they are modified by neural activity. The neural image of the visual scene that is processed by the retina and conducted to brain is the result of a complex interplay between excitation and inhibition. One source of inhibition in the retina is the input from horizontal cells onto photoreceptors and bipolar cells; another source is the input from glycinergic and GABAergic amacrine cells onto ganglion cells. In this proposed study the focus will be on characterizing the generation and modulation of inhibitory activity in these two pathways. The general approach is to characterize first the pharmacological and biophysical bases of cell-cell interactions and then incorporate these mechanisms into a more general model. For horizontal cells the study will be directed to investigating the mechanisms by which extracellular neurotransmitters, such as glutamate and GABA, and intracellular second messengers, particularly H+ ions, regulate function. For ganglion cells this project will characterize the action and mechanisms of glycinemediated inhibition in the tiger salamander and mouse retina. The study will utilize patch pipettes to perform voltage-clamp measurements from enzymatically-isolated retinal neurons. These same recording techniques will be used to measure light-evoked responses from neurons in the retinal slice preparation. Intracellular H+ and calcium ion activities will be monitored optically with selective dyes.